tbuckley/cabot-search huggingface dataset:
The parent penalty: Parental leave and return to work in trainees and early-career faculty in oncology.
Authors: Sindhu Janarthanam Malapati, Sunny R K Singh, Dame Idossa, Ximena Jordan Bruno, Fumiko Chino, Monica Arun Patel, Zihan Wei, Narjust Duma
Journal: Journal of Clinical Oncology (2022)

11005 Background: Prime childbearing years occur during medical training and early career, leaving physicians with tough choices between family planning and career growth. Restrictive parental leave (PL) policies can affect physician well-being and limit decisions about reproduction. We evaluated Medical and Radiation Oncology trainees and early career faculty to assess policies and practices regarding PL and return to work. Methods: An anonymous 48 question cross-sectional survey developed by researchers with expertise in gender equity was distributed via email and social media channels between May and June 2021 to oncology trainees and physicians within 5 years of terminal training. Descriptive statistics were used to compare study groups. Results: 255 physicians completed the survey- 54% female, 65% Medical Oncology and 35% Radiation Oncology, 71% trainees and 29% early career faculty. 46% (117) had no formal PL policy during training. PL impacted selection of first job for 37% (94) participants. Of all responders, 114 used PL, either in early career (18%), as a trainee (69%) or both (13%). Duration of PL during training was ≤4 weeks in 37%, 4-6 weeks in 19%, 6-8 weeks in 12% and ≥8 weeks in 24%. 27% of those who took PL as a trainee had to extend training to allow for this. Only 27%(31) of those who took PL had resources available at workplace to assist with transitioning back to work, primarily from informal mentoring by faculty/colleagues (65%, 20). Other important findings are summarized in the Table. Conclusions: In this study evaluating parental leave in oncology trainees and early faculty, almost half of the participants had no formal parental leave policy during training and majority of those who took parental leave during training had parental leave only for 6 weeks or less. Most participants experienced a parental leave penalty: guilt when seeking help and feeling overwhelmed at return to work. Policies and practices around parental leave need to be restructured to meet the needs of the evolving oncology workforce. [Table: see text]
Immune tumor microenvironnement (iTME) post-neoadjuvant chemotherapy, beyond PD-L1: Novel immune targets in ovarian cancer, data from the CHIVA trial, a GINECO/GINEGEPS study.
Authors: Felix Blanc-Durand, Elisa Yaniz-Galende, Catherine Genestie, Hortense Gauthier De Saint Basile, Laure Chardin, Gaetan De Rauglaudre, Nadia Raban, Annick Chevalier, Gwenael Ferron, Marie-Christine Kaminsky, Isabelle Laure Ray-Coquard, Salima Hamizi, Pierre Combe, Sophie Abadie Lacourtoisie, Florence Joly, Jérome Meunier, Anne Floquet, Jérôme Alexandre, Audrey Le Formal, Alexandra Leary
Journal: Journal of Clinical Oncology (2022)

5554 Background: Antibodies targeting PDL1 or PD1 have been disappointing so far in the treatment of ovarian cancer (OC). A greater understanding of the complex iTME and of the impact of chemotherapy on immune features could uncover promising immune targets. We previously reported that neoadjuvant chemotherapy (NACT) increased CD4+ and CD8+ immune cells (IC) and depleted FOXP3+ suppressive T-regs in OC iTME. Here we aimed to describe the expression of PDL1 as well as other co-regulatory molecules in OC and their changes under NACT. Methods: Tumor samples and clinical data were prospectively collected from patients (pts) in the randomized CHIVA trial of NACT +/- nintedanib. Samples were evaluable for immune profiling for 116-124 pts at diagnosis and 89-107 at surgery after 3 cycles of NACT. IC stained for CD4, CD8 were scored as number of IC+/mm². Expression of immune co-regulatory molecules PDL1, TIM3, LAG3 and IDO was scored as percentage of positive cells, and tumors were classified as PDL1/TIM3/IDO/LAG3 positive if &gt; 1% of IC and/or tumor cells (TC) were positive. Highly sensitive pts, defined as objective response to NACT and prolonged median progression-free survival (mPFS &gt; 24months), were compared to refractory pts (progressing during or within 3mo of platinum). Results: As expected, about one third (36%) of tumors were PDL1+ at diagnosis. In contrast, the prevalence of other co-regulatory molecules was higher with 52%, 54% and 93% of tumors being positive for IDO, LAG3 and TIM3, respectively. There was no significant change in PDL1 expression with NACT. However, in paired samples NACT significantly increased IDO and LAG3 expression (p &lt; 0.05), such that 60% and 66% of tumors post-NACT were positive for IDO and LAG3, respectively. TIM3 expression remained high post-NACT with 92% of positive tumors. Highly sensitive tumors (vs refractory tumors) had significantly higher IC expression of TIM3 after NACT (24% vs 6%, p = 0.005), and were significantly more infiltrated by CD4+ (441 vs 228 cells/mm2, p = 0.04) and CD8+ (460 vs 225 cells/mm2, p = 0.045) T cells. Conclusions: Other immune targets beyond PDL1 are highly expressed in OC. In addition NACT appears to prime the iTME by increasing effector T cell infiltration and the expression of other relevant co-regulatory molecules (LAG3, TIM3 and IDO). Future studies could be performed by priming the iTME with NACT and testing novel immune therapies based on target expression in samples obtained at interval debulking surgery.
Gender disparity in authorship of clinical trials leading to cancer drug approvals between 2008 and 2018: The glass ceiling of academic oncology.
Authors: Lynne O. Chapman, Jonathan M. Loree, Seerat Anand, Shehara Ramyalini Mendis, Lorna H McNeill, Kanwal Pratap Singh Raghav, Gauri Rajani Varadhachary
Journal: Journal of Clinical Oncology (2022)

11048 Background: Authorship, expressly premier positions (first, corresponding, or senior author), in peer reviewed journals is widely acknowledged as scientific credit in academia. Yet, gender inequities and biases pervade this facet of the scientific ecosystem. We reviewed the authorship of pivotal FDA trials that established the standards of care in oncology over the past decade with the goal of defining the magnitude of gender disparity in the most influential literature of the field in recent years. Methods: We collected and assessed data from the primary publication of 231 trials that enabled FDA drug approvals in hematology and oncology from July 2008 to June 2018. Author gender was assigned from listed names using statistical probability and confirmed using institutional websites and online databases (genderchecker database, biographical paragraphs, and social media). Authors where gender was not clearly identified (1.23%) were excluded. To account for equal authorship contribution, we included co-authors as distinct data points, and credit was given to reports for any women in premier authorship positions (first, corresponding, or senior author) to avoid overestimating disparity. Descriptive statistics were used, and 95% confidence intervals (95%CI) were reported using modified Wald method. Proportions were compared using Fisher-exact and Chi-squared test. Unadjusted P values of &lt; 0.05 were considered significant. Results: A total of 4664 (98.8%) authors were included in this analysis across 227 publications. Of these, 1287 (27.6%) were female with a median of 25.9% female authorship in total per trial. Female authorship was significantly higher for non-randomized (30.4% v 26.5% for randomized, P = 0.007) and phase 1/2 trials (29.9% v 26.3% for phase 3, P = 0.009) and varied with trial size (P &lt; 0.001), with the proportion greater in trials with ≤100 patients versus those with &gt; 500 patients. Female authorship in fields of breast and gynecological oncology was higher (41.3%) than other cancers (26.0%, P &lt; 0.001). Women were proportionally less likely to hold premier (9.2% v 18.2%, OR 0.46, 95%CI: 0.4 – 0.6, P &lt; 0.001), first (3.2% v 6.3%, OR 0.49, 95%CI: 0.3 – 0.7, P &lt; 0.001), senior (3.3% v 6.0%, OR 0.54, 95%CI: 0.4 – 0.8, P = 0.002) and corresponding (2.5% v 5.8%, OR 0.42, 95%CI 0.3 – 0.6, P &lt; 0.001) authorship but not second author role (4.1% v 5.1%, OR 0.80, 95%CI 0.6 – 1.1, P = 0.17). Conclusions: The under-representation of women in premier authorship positions in pivotal clinical trials, demonstrated in our study, serves as a barometer of a biased academic infrastructure, amplifying existing calls to address barriers that limit the full inclusion of women in oncology.
A cell-free RNA-based next-generation sequencing (NGS) assay for the detection of actionable gene fusions in patients with non–small cell lung cancer (NSCLC).
Authors: Yukti Choudhury, Chae Yin Cher, Jia Min Ho, Claire Chan, Mun Wei Teh, Kao Chin Ngeow, Michelle Pek
Journal: Journal of Clinical Oncology (2022)

3040 Background: Gene fusions and alternate RNA splice forms represent clinically actionable driver and resistance-conferring alterations in NSCLC and other cancers. Where tissue samples are inadequate for molecular testing, liquid biopsies could address the gap in detection of clinically relevant gene fusions. Targeted cell-free (cf) DNA-based NGS methods are typically used for non-invasive blood-based testing of gene fusions, but have limited sensitivity if fusion breakpoints involve long intronic regions or repetitive sequences (e.g. NTRKs and NRG1). RNA-based approaches are not affected by introns, can identify expressed fusion genes and can discriminate splicing. We developed an NGS assay optimized for cfRNA analyte for the detection of actionable gene fusions and exon deletion/skipping events in liquid biopsies. Methods: A highly multiplexed molecular-barcoded primer panel was designed for cfRNA-based detection of actionable fusion genes in NSCLC ( ALK, BRAF, FGFR2, FGFR3, MET (including exon 14 skipping), NRG1, NTRK1/2/3, RET and ROS1) covering &gt; 90% of reported driver and partner gene exons in COSMIC database. The panel also targets housekeeping genes as endogenous sample controls. We developed a custom bioinformatics pipeline to call fusions and exon skipping based on split and spanning reads. Results: In initial analytical validation using fragmented RNA from pre-characterized reference material (representing 32 unique fusions at known copy numbers), the assay could detect as low as 10 fusion copies with a sensitivity of 97.6% and a specificity of 100%. For clinical testing, cfRNA co-eluted with cfDNA in nucleic acid extracts from plasma was used. In plasma samples (n = 103) from advanced NSCLC, 76% (15/21) of fusions (5 ALK, 3 RET, 2 ROS1, 5 MET ex14 skipping, 1 FGFR3-TACC3) detected in a clinically validated cfDNA assay (LiquidHALLMARK) were also detected in corresponding cfRNA. In a subset of samples that were driver-negative untreated or tyrosine kinase-inhibitor treated, the cfRNA assay yielded 9 gene fusions or breakpoints (1 CD74-NRG1, 4 BRAF, 2 MET, 2 FGFR3-TACC3 fusions) that could not be detected by the cfDNA assay. This represents an increase of 8.7% (9/103) of actionable alterations (driver or resistance) identified using cfRNA. Together cfRNA and cfDNA resulted in 30 fusion events to be detected compared to 21 by the cfDNA assay alone, representing a 42.8% (9/21) increase in fusion-specific detection of the combined assay. Conclusions: This novel cfRNA assay can detect actionable gene fusions and exon skipping events in liquid biopsies with high sensitivity. Combining cfRNA with more routine cfDNA testing can increase the total actionable diagnostic information from non-invasive testing in NSCLC patients where tissue samples are lacking, especially for gene fusions not amenable to detection in cfDNA.
Efficacy and safety of SER-109, an investigational microbiome therapeutic for recurrent <i>clostridioides difficile</i> infection: Data from ECOSPOR III, a phase 3 randomized trial.
Authors: Alla Paskovaty, Charles S. Berenson, Thomas J. Louie, Elaine Wang, David A. Lombardi, Lisa von Moltke
Journal: Journal of Clinical Oncology (2022)

12113 Background: Patients with malignancies are at increased risk for recurrent Clostridioides difficile infection (rCDI) due to their immunosuppressed state and frequent exposure to antibiotics and chemotherapy. These factors disrupt the gut microbiome creating an environment conducive to C. difficile colonization. Patients with cancer have higher rates of rCDI and worse outcomes than those without malignancy. SER-109, an investigational microbiome therapeutic, was superior to placebo in reducing rCDI at 8 weeks compared with placebo (12% vs 40%, respectively) in ECOSPOR III, a Phase 3 randomized, double-blind trial of subjects with a history of rCDI [NEJM 2022; 386:220-9]. Here, we report secondary endpoints of rCDI rates at 4, 12 and 24 weeks. Methods: Adults with rCDI (≥3 episodes in 12 months) were screened at 56 US/Canadian sites. After standard-of-care antibiotics (vancomycin or fidaxomicin per investigator discretion), subjects were randomized 1:1 to SER-109 (4 capsules x 3 days) or matching placebo. The primary endpoint was rCDI (recurrent toxin + diarrhea requiring treatment) at 8 weeks; secondary endpoints included rCDI at 4, 12 and 24 weeks. Safety was evaluated through week 24. Results: 281 subjects were screened and 182 (intention-to-treat population; ITT) were randomized (59.9% female; mean age 65.5 years). The most common comorbidities were respiratory disease (36.3%) and cardiovascular disease (32.4%). A total of 28.6% and 18.1% had a history of immunocompromise and malignancy, respectively. Significantly fewer SER-109 vs. placebo treated subjects had rCDI posttreatment compared with placebo recipients at Weeks 4, 8, 12 and 24 (Table). The absolute risk reduction between placebo and SER-109 arms ranged from 22.1% to 28.3% across the 4 timepoints. The safety profile of SER-109 through week 24 was comparable to placebo. Most adverse events (AEs) were mild to moderate gastrointestinal occurrences. More placebo-treated vs SER-109-treated subjects experienced serious AEs through week 8, while comparable proportions of subjects in both arms reported serious AEs from 8 through 24 weeks. Conclusions: In this population of subjects with comorbidities, including malignancy and immunosuppression, SER-109 significantly reduced rCDI rates through week 24 with an observed safety profile comparable to placebo. Clinical trial information: NCT03183128. [Table: see text]
Association between environmental quality index and young onset colorectal cancer.
Authors: Suleyman Yasin Goksu, Jude Khatib, Sarah Reddy, Muhammet Ozer, Mary Claire Maxwell, Leticia Khosama, Radhika Kainthla, Nina Niu Sanford, Javier Salgado Pogacnik, Sitaram Chilakamarry, Emina Huang, Shaalan Shaalan Beg, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2022)

3548 Background: The factors associated with the rise of young-onset colorectal cancer (YOCRC) remain unclear. However, environmental exposures are believed to be associated with YOCRC in addition to hereditary factors. Therefore, we evaluated the association between the national level Environmental Quality Index (EQI) and YOCRC in the US. Methods: We queried the SEER database to identify adult colorectal cancer patients diagnosed between 2010-2016. YOCRC was defined as age at diagnosis &lt; 50 years. EQI (2005-2010) is a measure of county-level cumulative environmental exposures that includes 5 domains: sociodemographic, built, air, land, and water. A higher value represents a lower environmental quality. We distributed the total EQI and each EQI domain into five quintiles. Multivariable logistic regression analysis was used to assess the relationship between YOCRC and quintiles (upper-most vs. lowest) of EQI after adjusting by race (White, Black, and Others), gender, and stage at diagnosis. The age-adjusted incidence rate was also calculated using the SEER*Stat, and correlation efficiency was estimated between EQI domains and incidence rate. Results: A total of 261,417 CRC patients were included; 11% were YOCRC. In the adjusted multivariable analysis, poor built EQI (OR 1.15 [1.11-1.20]) and water EQI (OR 1.08 [1.03-1.12]) were more likely to be associated with YOCRC. Poor built EQI was more strongly associated with Black YOCRC (OR 1.21 [1.09-1.35]) as compared to White YOCRC (OR 1.14 [1.09-1.19]). Poor sociodemographic EQI was more strongly associated with Others (OR 1.47 [1.25-1.72]) compared to Black YOCRC (OR 1.14 [1.03-1.25]). In addition, poor built EQI (OR 1.19 [1.12-1.27]) and water EQI (OR 1.12 [1.05-1.19]) were more strongly associated with the metastatic disease among YOCRC patients. However, the total poor EQI was not associated with YOCRC (OR 0.99 [0.95-1.03]). On incidence analysis, there was a positive correlation between the incidence rate of YOCRC and sociodemographic EQI (rho = 0.49, p &lt; 0.001), air EQI (rho = 0.30, p &lt; 0.001), and land EQI (rho = 0.18, p &lt; 0.001). Conclusions: This study evaluated a population-based ecological approach and showed that YOCRC was associated with lower environmental quality, including built and water domains. EQI domains were also associated with different racial groups among YOCRC. Instead of studying single environmental exposures, the impact of the cumulative environmental index should be recognized and studied further to understand the mechanism of cancer development.
Impact of age and gender on the efficacy and safety of panitumumab plus fluorouracil and folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS WT metastatic colorectal cancer (mCRC): Subgroup analysis of the PANAMA-study (AIO-KRK-0212).
Authors: Kathrin Heinrich, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Lothar Müller, Alexander Koenig, Ludwig von Weikersthal, Karel Caca, Albrecht Kretzschmar, Eray Goekkurt, Siegfried Haas, Annabel Helga Sophie Alig, Annika Kurreck, Arndt Stahler, Swantje Held, Anke C. Reinacher-Schick, Volker Heinemann, Sebastian Stintzing, Tanja Trarbach, Dominik Paul Modest
Journal: Journal of Clinical Oncology (2022)

3567 Background: Clinical trials in mCRC are usually conducted irrespective of gender and mostly also irrespective of age. However, gender- and age-associated differences relating to safety and efficacy in the treatment of mCRC are of presently moving into the focus of interest. We investigated the effect of gender and age on efficacy and safety in the PANAMA trial. Methods: PANAMA investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type metastatic colorectal cancer. In this post-hoc analysis, the study population was stratified for age (≤ 65 years versus &gt; 65 years) and gender (male versus female). Evaluated efficacy endpoints were progression-free survival (PFS), overall survival (OS) of maintenance therapy and objective response rate (ORR) during maintenance therapy. Safety endpoints were rates of any grade and grade 3/4 adverse events (AEs). Results: In total, 165 male and 83 female patients were randomized and treated. Male patients had a significant benefit from the addition of Pmab to maintenance treatment with regard to PFS (HR 0.63; 95% CI 0.45-0.88; p = 0.006) and demonstrated a strong trend towards better ORR during maintenance therapy (Odds ratio 1.92; 95%CI 1.02-3.70, p = 0.053). In female patients, no difference regarding PFS was seen between treatment arms (HR 0.85; 95% CI 0.53-1.35, p = 0.491), while a trend towards better ORR with Pmab (Odds ratio 2.50; 95% CI 0.99-6.25; p = 0.063) was observed. Gender had no significant impact on OS, nor did age categories affect survival endpoints. Adverse events grade ≥ 3 occurring during maintenance therapy were comparable between male and female patients (12.9% vs 13.5%; p = 0.791) and in different age categories (p = 0.393). Conclusions: In the Panama trial, addition of Pmab to maintenance treatment with FU/FA improved outcome in RAS wild-type mCRC. This effect is irrespective of age and is pronounced in male patients. Our results support the relevance of gender in mCRC. Clinical trial information: NCT01991873. [Table: see text]
The impact of vertical integration of oncologists on cancer outcomes and healthcare costs among metastatic prostate cancer patients.
Authors: Xin Hu, Joseph Lipscomb, Ilana Graetz
Journal: Journal of Clinical Oncology (2022)

e18786 Background: The share of oncology practices that were vertically integrated with hospitals more than doubled in the past decade. Vertical integration leads to higher spending, but evidence on quality and outcomes remains inconclusive. This study examines how integration between hospitals and oncologists affects patient outcomes and spending among patients with metastatic prostate cancer. Methods: Using the SEER-Medicare linkage with the Medicare Data on Provider Practice and Specialty file, we identified Medicare beneficiaries diagnosed with metastatic, castration-resistant prostate cancer who initiated chemotherapy between 2008-2017 (n = 9,167). We used a claims-based approach to identify treating oncologists and their integration status (as indexed by percent of total services billed to hospital outpatient departments). Outcomes included: 1) time on chemotherapy, 2) survival from chemotherapy initiation, 3) supportive care use (i.e. bone-modifying agents [BMA]), 4) Medicare payment for the first 3 months of chemotherapy initiation and last 3 months before end of life (EOL). The differences-in-differences approach was used to compare patient outcomes before and after oncologists became integrated versus those whose oncologists remained non-integrated or always integrated. Weibull survival and linear models were used for regression analysis, adjusting for sociodemographic, clinical, and market characteristics. Results: The proportion of patients treated by integrated oncologists increased from 28% in 2008 to 55% in 2017. Vertical integration was associated with 13.6 percentage points increase (95% CI = 6.1 to 21.1) in the likelihood of BMA use, but no significant changes for time on chemotherapy and survival. Average Medicare spending in the first 3 months of chemotherapy initiation and last 3 months of EOL was $34,324 and $42,624, respectively. Vertical integration did not have a significant effect on overall spending. Further decomposition showed decreases in professional service costs (-$4,264, 95% CI = -$6,642 to -$1,887) along with an increase in outpatient care costs ($3,941, 95% CI = $159 to $7,723) for the first 3 months of chemotherapy. A similar pattern was found for spending in the last 3 months of EOL. Conclusions: Vertical integration of oncologists was associated with increased use of supportive care, but not time on chemotherapy or survival among metastatic prostate cancer patients. Although oncologists switched service billing from physician offices to hospital outpatient departments, we did not detect significant increases in total Medicare spending after vertical integration. This suggests the potential for quality improvement following vertical integration without substantial increases in healthcare spending. Future studies should extend the investigation to other cancer types and patient outcomes.